Reversibility of Age-related Oxidized Free NADH Redox States in Alzheimer's Disease Neurons by Imposed External Cys/CySS Redox Shifts

Scientific Reports
Yue DongGregory J Brewer

Abstract

Redox systems including extracellular cysteine/cystine (Cys/CySS), intracellular glutathione/oxidized glutathione (GSH/GSSG) and nicotinamide adenine dinucleotide reduced/oxidized forms (NADH/NAD+) are critical for maintaining redox homeostasis. Aging as a major risk factor for Alzheimer's disease (AD) is associated with oxidative shifts, decreases in anti-oxidant protection and dysfunction of mitochondria. Here, we examined the flexibility of mitochondrial-specific free NADH in live neurons from non-transgenic (NTg) or triple transgenic AD-like mice (3xTg-AD) of different ages under an imposed extracellular Cys/CySS oxidative or reductive condition. We used phasor fluorescence lifetime imaging microscopy (FLIM) to distinguish free and bound NADH in mitochondria, nuclei and cytoplasm. Under an external oxidative stress, a lower capacity for maintaining mitochondrial free NADH levels was found in old compared to young neurons and a further decline with genetic load. Remarkably, an imposed Cys/CySS reductive state rejuvenated the mitochondrial free NADH levels of old NTg neurons by 71% and old 3xTg-AD neurons by 89% to levels corresponding to the young neurons. Using FLIM as a non-invasive approach, we were able to measure the re...Continue Reading

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Citations

Nov 28, 2019·Journal of Alzheimer's Disease : JAD·Gregory J BrewerCharles G Glabe
May 22, 2021·Aging·Yue DongGregory J Brewer
Sep 10, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Ying-Ji Sun, Chao Yu
Sep 9, 2021·Proceedings of the National Academy of Sciences of the United States of America·Takayuki TeruyaMitsuhiro Yanagida

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Methods Mentioned

BETA
fluorescence imaging
imaging technique
transgenic
genotyping

Software Mentioned

SPSS Statistics
Excel
Stringari
SimFCS

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